Paving the way to FDA? tips and pitfalls. The Nextar start up support program Dr. Orna Dreazen- CEO

Transcription

1 Paving the way to FDA? tips and pitfalls The Nextar start up support program Dr. Orna Dreazen- CEO

2 Drug Development Process Discovery Development Commercial Market Basic Research Pre-Clinical Clinical Testing Marketing I II III IV Product Launch Sales IND NDA

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4 Drug Development in the U.S. 10,000 Compounds evaluated in pre-clinical testing only 250 are ever tested in human subjects 1 Marketed Product

5 Kinetics of Drug Development Process

6 Pharmaceutical Development ICH Q8 (R2) We are a start-up we don t need it! True?

7 Q8 - Forward An opportunity to present the knowledge gained through the application of scientific approaches and quality risk management (for definition, see ICH Q9) to the development of a product and its manufacturing process. The aim of pharmaceutical development is to design a quality product and its manufacturing process to consistently deliver the intended performance of the product.

8 ICH Q8 (R2) Quality cannot be tested into products Quality should be built in by design Changes in formulation and manufacturing processes during development and lifecycle management should be looked upon as opportunities to gain additional knowledge and further support establishment of the design space.

9 ICH Q8 (R2) Inclusion of relevant knowledge gained from experiments giving unexpected results can also be useful Design space is proposed by the applicant and is subject to regulatory assessment and approval. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process.

10 Objectives Achieve Product Realization Establish and Maintain a State of Control Facilitate Continual Improvement Knowledge Management

11 Sources of knowledge include: Innovation Prior knowledge Pharmaceutical development studies Technology transfer activities Process validation studies over the product lifecycle Manufacturing experience Continual improvement Change management activities.

12 What are the key factors for success? Good & Commited management Openness to new ideas Focus Clear strategy Transparency with your investors and collaborators Risk management

13 Quality Risk Management It can provide a proactive approach to: Identifying Scientifically evaluating and Controlling potential risks to quality. The design, organization and documentation of the pharmaceutical quality system should be well structured and clear to facilitate common understanding and consistent application.

14 Risk Assessment The elements of cgmp should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognizing the different goals and knowledge available for each stage. The pharmaceutical quality system should include appropriate processes, resources and responsibilities to provide assurance of the quality of outsource activities and purchased materials. Management responsibilities should be identified within the pharmaceutical quality system.

15 Risk evaluation questions Risk= Occurrence x severity x detectability 1. What is the probability it will go wrong? 2. What is the severity (consequences)? 3. Can I detect the harm easily?

16 Main goal of risk management Risk control Process in which decisions are made and measures implemented by which risks are reduced to, or maintained within specified preferred and tolerable levels.

17 Management Commitment Senior management has the ultimate responsibility to ensure an effective pharmaceutical quality system is in place in achieve the quality objectives, and that roles, responsibilities, and authorities are defined, communicated and implemented throughout the company. Management should: Participate in the design, implementation, monitoring and maintenance of an effective pharmaceutical quality system;

18 Management Commitment Demonstrate strong and visible support for the pharmaceutical quality system and ensure its implementation throughout their organization; Ensure that a timely and effective communication and escalation process exists to raise quality issues to the appropriate levels of management.

19 How do you maximize the potential to develop a product? Experimental design Use high quality materials Repeat experiments and make sure they are reproducible Risk management

20 How do you maximize the potential to develop a product (2) Document, document, document Provide rational for the design Document detailed experimental protocol Raw data and all calculations Conclusions from the experiment Rational for the next experiment

21 Development of a new product Basic research Protection of IP Formulation development Toxicological studies Production process development Production scale-up Production of clinical trial material (CTM)

22 Development of drug product- Cont. Development of analytical methods Stability studies Clinical trials Bio-analysis CMC Regulatory submission.

23 What have we learnt? GMP directives focus on patient s safety A start-up doesn t need to be certified A start-up may learn a lot from the GMP directives The developing organization must work in compliance with cgmp

24 Early stage limitations Scarce resources Limited experience in developing new drugs Complicated developmental processrequires expertise in many different aspects Limited understanding in regulatory requirements Impatient investors

25 What are the needs of most startups? Expertise in formulation Technical engineering know how Production knowledge and facilities Analytical knowledge for development and validation of procedures Infrastructure operating in compliance with GLP and GMP

26 Common Technological Limitations Process was developed in a small laboratory scale The process may not be repeated in industrial setting Un optimized process The patenting process is complicated and unclear Active material is expensive and thus limited

27 Common Technological Limitations- cont. Consulting many experts some time contradicting advice Unclear indications Regulations from different authorities are confusing and demanding Limited knowledge about the drug product

28 Possible solutions Consult different consultants for each aspect Use an outsourcing one stop shop Establish your own laboratory Join an incubator

29 Who is Nextar? Outsourcing company providing full integrated contract drug development and manufacturing (CDMO) Equipped with state of the art laboratories and sterile clean rooms Based at the Weizmann Science Park 33 employees

30 Achievements since 2007 (establishment) Served app. 50% of the Israeli life sciences start ups Over 1000 projects were performed Over 200 customers Performed various projects for Big Pharma (both local and international) Developed over 60 innovative manufactured for clinical trials, in Israel and worldwide

31 Certifications cgmp - by the Israeli Ministry of Health which is recognized also by EU /PIC/s OECD GLP ISO by SII (member of IQnet)

32 Creating Value for investors Nextar might be interested to invest in your Start-up subject to its evaluation. Investment can reach 20% of a project cost (subject to the fund rules and regulations) Investors are required to put less capital Burn rate goes down, the start-up can do more with same capital Risk is incrementally shared

33 How does it work? NIS 500,000 project Nextar Chempharma Solutions Ltd. Selected Start-Up Ltd. Investment in shares NIS 100,000 Payment NIS 500,000 Nextar Ventures Project Financing Chief Scientist 50% Portfolio Investors 30% Nextar 20% Start-Up 4 Ltd.

34 Thanks for listening! We at Nextar shall be happy to assist you Dr. Orna Dreazen